Evidence linking exposure of fish primary macrophages to antibiotics activates the NF-kB pathway.

Low doses of antibiotics are ubiquitous in the marine environment and may exert negative effects on non-target aquatic organisms. Using primary macrophages of common carp, we investigated the mechanisms of action following exposure to several common antibiotics; cefotaxime, enrofloxacin, tetracycline, sulfamonomethoxine, and their mixtures, and explored the immunomodulatory effects associated with the nuclear factor-κB (NF-κB) signaling pathway. A KEGG pathway analysis was conducted using the sixty-six differentially expressed genes found in all treatments, and showed that exposure to 100 μg/L of antibiotics could affect regulation of the NF-κB signaling pathway, suggesting that activation of NF-κB is a common response in all four classes of antibiotics. In addition, the four antibiotics induced nf-κb and NF-κB-associated cytokines expression, as verified by qPCR, however, these induction responses by four antibiotics were minor when compared to the same concentration of LPS treatment (100 μg/L). Antagonists of NF-κB blocked many of the immune effects of the antibiotics, providing evidence that NF-κB pathways mediate the actions of all four antibiotics. Moreover, exposure to environmentally relevant, low levels (0.01-100 μg/L) of antibiotics induced a NF-κB-mediated immune response, including endogenous generation of ROS, activity of antioxidant enzymes, as well as expression of cytokine and apoptosis. Moreover, exposure to mixtures of antibiotics presented greater effects on most tested immunological parameters than exposure to a single antibiotic, suggesting additive effects from multiple antibiotics in the environment. This study demonstrates that exposure of fish primary macrophages to low doses of antibiotics activates the NF-kB pathway

Delayed antibiotic prescriptions for respiratory infections

Background: Concerns exist regarding antibiotic prescribing for respiratory tract infections (RTIs) owing to adverse reactions, cost, and antibacterial resistance. One proposed strategy to reduce antibiotic prescribing is to provide prescriptions, but to advise delay in antibiotic use with the expectation that symptoms will resolve first. This is an update of a Cochrane Review originally published in 2007, and updated in 2010 and 2013. Objectives: To evaluate the effects on clinical outcomes, antibiotic use, antibiotic resistance, and patient satisfaction of advising a delayed prescription of antibiotics in respiratory tract infections. Search methods: For this 2017 update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 4, 2017), which includes the Cochrane Acute Respiratory Infection Group's Specialised Register; Ovid MEDLINE (2013 to 25 May 2017); Ovid Embase (2013 to 2017 Week 21); EBSCO CINAHL Plus (1984 to 25 May 2017); Web of Science (2013 to 25 May 2017); WHO International Clinical Trials Registry Platform (1 September 2017); and ClinicalTrials.gov (1 September 2017). Selection criteria: Randomised controlled trials involving participants of all ages defined as having an RTI, where delayed antibiotics were compared to immediate antibiotics or no antibiotics. We defined a delayed antibiotic as advice to delay the filling of an antibiotic prescription by at least 48 hours. We considered all RTIs regardless of whether antibiotics were recommended or not. Data collection and analysis: We used standard Cochrane methodological procedures. Three review authors independently extracted and collated data. We assessed the risk of bias of all included trials. We contacted trial authors to obtain missing information. Main results: For this 2017 update we added one new trial involving 405 participants with uncomplicated acute respiratory infection. Overall, this review included 11 studies with a total of 3555 participants. These 11 studies involved acute respiratory infections including acute otitis media (three studies), streptococcal pharyngitis (three studies), cough (two studies), sore throat (one study), common cold (one study), and a variety of RTIs (one study). Five studies involved only children, two only adults, and four included both adults and children. Six studies were conducted in a primary care setting, three in paediatric clinics, and two in emergency departments. Studies were well reported, and appeared to be of moderate quality. Randomisation was not adequately described in two trials. Four trials blinded the outcomes assessor, and three included blinding of participants and doctors. We conducted meta-analysis for antibiotic use and patient satisfaction. We found no differences among delayed, immediate, and no prescribed antibiotics for clinical outcomes in the three studies that recruited participants with cough. For the outcome of fever with sore throat, three of the five studies favoured immediate antibiotics, and two found no difference. For the outcome of pain related to sore throat, two studies favoured immediate antibiotics, and three found no difference. One study compared delayed antibiotics with no antibiotic for sore throat, and found no difference in clinical outcomes. Three studies included participants with acute otitis media. Of the two studies with an immediate antibiotic arm, one study found no difference for fever, and the other study favoured immediate antibiotics for pain and malaise severity on Day 3. One study including participants with acute otitis media compared delayed antibiotics with no antibiotics and found no difference for pain and fever on Day 3. Two studies recruited participants with common cold. Neither study found differences for clinical outcomes between delayed and immediate antibiotic groups. One study favoured delayed antibiotics over no antibiotics for pain, fever, and cough duration (moderate quality evidence for all clinical outcomes - GRADE assessment). There were either no differences for adverse effects or results favoured delayed antibiotics over immediate antibiotics (low quality evidence - to GRADE assessment) with no significant differences in complication rates. Delayed antibiotics resulted in a significant reduction in antibiotic use compared to immediate antibiotics prescription (odds ratio (OR) 0.04, 95% confidence interval (CI) 0.03 to 0.05). However, a delayed antibiotic was more likely to result in reported antibiotic use than no antibiotics (OR 2.55, 95% CI 1.59 to 4.08) (moderate quality evidence - GRADE assessment). Patient satisfaction favoured delayed over no antibiotics (OR 1.49, 95% CI 1.08 to 2.06). There was no significant difference in patient satisfaction between delayed antibiotics and immediate antibiotics (OR 0.65, 95% CI 0.39 to 1.10) (moderate quality evidence - GRADE assessment). None of the included studies evaluated antibiotic resistance. Authors' conclusions: For many clinical outcomes, there were no differences between prescribing strategies. Symptoms for acute otitis media and sore throat were modestly improved by immediate antibiotics compared with delayed antibiotics. There were no differences in complication rates. Delaying prescribing did not result in significantly different levels of patient satisfaction compared with immediate provision of antibiotics (86% versus 91%) (moderate quality evidence). However, delay was favoured over no antibiotics (87% versus 82%). Delayed antibiotics achieved lower rates of antibiotic use compared to immediate antibiotics (31% versus 93%) (moderate quality evidence). The strategy of no antibiotics further reduced antibiotic use compared to delaying prescription for antibiotics (14% versus 28%). Delayed antibiotics for people with acute respiratory infection reduced antibiotic use compared to immediate antibiotics, but was not shown to be different to no antibiotics in terms of symptom control and disease complications. Where clinicians feel it is safe not to prescribe antibiotics immediately for people with respiratory infections, no antibiotics with advice to return if symptoms do not resolve is likely to result in the least antibiotic use while maintaining similar patient satisfaction and clinical outcomes to delaying prescription of antibiotics. Where clinicians are not confident in using a no antibiotic strategy, a delayed antibiotics strategy may be an acceptable compromise in place of immediate prescribing to significantly reduce unnecessary antibiotic use for RTIs, and thereby reduce antibiotic resistance, while maintaining patient safety and satisfaction levels. Editorial note: As a living systematic review, this review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review

Prolonged duration of early antibiotic therapy in extremely premature infants.

BackgroundProlonged early antibiotics in extremely premature infants may have negative effects. We aimed to assess prevalence and outcomes of provision of prolonged early antibiotics to extremely premature infants in the absence of culture-confirmed infection or NEC.MethodsCohort study of infants from 13 centers born without a major birth defect from 2008-2014 who were 401-1000 grams birth weight, 22-28 weeks gestation, and survived ≥5 days without culture-confirmed infection, NEC, or spontaneous intestinal perforation. We determined the proportion of infants who received prolonged early antibiotics, defined as ≥5 days of antibiotic therapy started at ≤72 h of age, by center and over time. Associations between prolonged early antibiotics and adverse outcomes were assessed using multivariable logistic regression.ResultsA total of 5730 infants were included. The proportion of infants receiving prolonged early antibiotics varied from 30-69% among centers and declined from 49% in 2008 to 35% in 2014. Prolonged early antibiotics was not significantly associated with death (adjusted odds ratio 1.17 [95% CI: 0.99-1.40], p = 0.07) and was not associated with NEC.ConclusionsThe proportion of extremely premature infants receiving prolonged early antibiotics decreased, but significant center variation persists. Prolonged early antibiotics were not significantly associated with increased odds of death or NEC

Prevalence and predictors of postdischarge antibiotic use following mastectomy

OBJECTIVESurvey results suggest that prolonged administration of prophylactic antibiotics is common after mastectomy with reconstruction. We determined utilization, predictors, and outcomes of postdischarge prophylactic antibiotics after mastectomy with or without immediate breast reconstruction.DESIGNRetrospective cohort.PATIENTSCommercially insured women aged 18–64 years coded for mastectomy from January 2004 to December 2011 were included in the study. Women with a preexisting wound complication or septicemia were excluded.METHODSPredictors of prophylactic antibiotics within 5 days after discharge were identified in women with 1 year of prior insurance enrollment; relative risks (RR) were calculated using generalized estimating equations.RESULTSOverall, 12,501 mastectomy procedures were identified; immediate reconstruction was performed in 7,912 of these procedures (63.3%). Postdischarge prophylactic antibiotics were used in 4,439 procedures (56.1%) with immediate reconstruction and 1,053 procedures (22.9%) without immediate reconstruction (P&lt;.001). The antibiotics most commonly prescribed were cephalosporins (75.1%) and fluoroquinolones (11.1%). Independent predictors of postdischarge antibiotics were implant reconstruction (RR, 2.41; 95% confidence interval [CI], 2.23–2.60), autologous reconstruction (RR, 2.17; 95% CI, 1.93–2.45), autologous reconstruction plus implant (RR, 2.11; 95% CI, 1.92–2.31), hypertension (RR, 1.05; 95% CI, 1.00–1.10), tobacco use (RR, 1.07; 95% CI, 1.01–1.14), surgery at an academic hospital (RR, 1.14; 95% CI, 1.07–1.21), and receipt of home health care (RR, 1.11; 95% CI, 1.04–1.18). Postdischarge prophylactic antibiotics were not associated with SSI after mastectomy with or without immediate reconstruction (bothP&gt;.05).CONCLUSIONSProphylactic postdischarge antibiotics are commonly prescribed after mastectomy; immediate reconstruction is the strongest predictor. Stewardship efforts in this population to limit continuation of prophylactic antibiotics after discharge are needed to limit antimicrobial resistance.Infect Control Hosp Epidemiol2017;38:1048–1054</jats:sec

"Practical Knowledge" and Perceptions of Antibiotics and Antibiotic Resistance Among Drugsellers in Tanzanian Private Drugstores.

Studies indicate that antibiotics are sold against regulation and without prescription in private drugstores in rural Tanzania. The objective of the study was to explore and describe antibiotics sale and dispensing practices and link it to drugseller knowledge and perceptions of antibiotics and antibiotic resistance. Exit customers of private drugstores in eight districts were interviewed about the drugstore encounter and drugs bought. Drugsellers filled in a questionnaire with closed- and open-ended questions about antibiotics and resistance. Data were analyzed using mixed quantitative and qualitative methods. Of 350 interviewed exit customers, 24% had bought antibiotics. Thirty percent had seen a health worker before coming and almost all of these had a prescription. Antibiotics were dispensed mainly for cough, stomachache, genital complaints and diarrhea but not for malaria or headache. Dispensed drugs were assessed as relevant for the symptoms or disease presented in 83% of all cases and 51% for antibiotics specifically. Non-prescribed drugs were assessed as more relevant than the prescribed. The knowledge level of the drugseller was ranked as high or very high by 75% of the respondents. Seventy-five drugsellers from three districts participated. Seventy-nine percent stated that diseases caused by bacteria can be treated with antibiotics but 24% of these also said that antibiotics can be used for treating viral disease. Most (85%) said that STI can be treated with antibiotics while 1% said the same about headache, 4% general weakness and 3% 'all diseases'. Seventy-two percent had heard of antibiotic resistance. When describing what an antibiotic is, the respondents used six different kinds of keywords. Descriptions of what antibiotic resistance is and how it occurs were quite rational from a biomedical point of view with some exceptions. They gave rise to five categories and one theme: Perceiving antibiotic resistance based on practical experience. The drugsellers have considerable "practical knowledge" of antibiotics and a perception of antibiotic resistance based on practical experience. In the process of upgrading private drugstores and formalizing the sale of antibiotics from these outlets in resource-constrained settings, their "practical knowledge" as well as their perceptions must be taken into account in order to attain rational dispensing practices

Antibiotic prescribing by general dental practitioners in the Greater Glasgow Health Board, Scotland

OBJECTIVE: To investigate antibiotic prescribing patterns by general dental practitioners (GDPs) in the Greater Glasgow Health Board Area, Scotland. STUDY DESIGN: A 10% sample of prescriptions were selected at random from 35,545 prescriptions written by GDPs over a 6-month period. MAIN OUTCOME MEASURES: Absolute and relative frequencies were used to describe the different classes of antibiotics used and the variations in prescribing practice. RESULTS: GDPs prescribed a wide range of antibiotics. Seventeen different antibiotics were prescribed with amoxycillin, metronidazole and penicillin V accounting for almost 90% of the prescriptions. In general the antibiotics were prescribed at the British National Formulary (BNF) recommended doses. There were, however, wide variations in the frequencies and durations of the prescriptions for all antibiotics. CONCLUSIONS: The present study provides evidence of sub-optimal prescribing of antibiotics by dentists in Scotland, with considerable variation from the recommended frequencies and doses

The path of least resistance: Paying for antibiotics in non-human uses

Antibiotic resistance is a critical threat to human and animal health. Despite the importance of antibiotics, regulators continue to allow antibiotics to be used in low-value applications - subtherapeutic dosing in animals, and spraying tobacco plants for blue mold, for example - where the benefits are unlikely to outweigh the costs in terms of increased resistance. We explore the application of a user fee in non-human uses of antibiotics. Such a fee would efficiently deter low value uses while also providing funding to support the development of the urgently needed new antibiotics

Growth Performance of Holstein Dairy Calves Supplemented with a Probiotic

Administration of antibiotics in both therapeutic and sub-therapeutic doses has been the standard practice for dealing with pathogenic bacteria problems in farm animals since the 1940s. Several types of antibiotics are currently used to promote weight gain and feed efficiency in domestic livestock. There is growing concern that the use of antibiotics as growth promoters may result in the development of resistant populations of pathogenic bacteria and, in turn, influence the therapeutic use of antibiotics. The indiscriminate and improper use of antibiotics in food-producing animals could result in the presence of residues in milk, meat, and other animal food products consumed by humans. One possible alternative to antibiotics is the use of probiotics. Probiotics can be defined as “live microbial feed supplements which beneficially affect the host animal by improving its intestinal microbial balance” (Fuller, 1989). Probiotics introduce beneficial microorganisms into the gut which act to maintain optimal conditions within the gastrointestinal tract and inhibit the growth of pathogenic or other undesirable bacteria

Measuring antibiotic availability and use in 20 low- and middle-income countries

Objective To assess antibiotic availability and use in health facilities in low- and middle-income countries, using the service provision assessment and service availability and readiness assessment surveys. Methods We obtained data on antibiotic availability at 13 561 health facilities in 13 service provision assessment and 8 service availability and readiness assessment surveys. In 10 service provision assessment surveys, child consultations with health-care providers were observed, giving data on antibiotic use in 22 699 children. Antibiotics were classified as access, watch or reserve, according to the World Health Organization’s AWaRe categories. The percentage of health-care facilities across countries with specific antibiotics available and the proportion of children receiving antibiotics for key clinical syndromes were estimated. Findings The surveys assessed the availability of 27 antibiotics (19 access, 7 watch, 1 unclassified). Co-trimoxazole and metronidazole were most widely available, being in stock at 89.5% (interquartile range, IQR: 11.6%) and 87.1% (IQR: 15.9%) of health facilities, respectively. In contrast, 17 other access and watch antibiotics were stocked, by fewer than a median of 50% of facilities. Of the 22 699 children observed, 60.1% (13 638) were prescribed antibiotics (mostly co-trimoxazole or amoxicillin). Children with respiratory conditions were most often prescribed antibiotics (76.1%; 8972/11 796) followed by undifferentiated fever (50.1%; 760/1518), diarrhoea (45.7%; 1293/2832) and malaria (30.3%; 352/1160). Conclusion Routine health facility surveys provided a valuable data source on the availability and use of antibiotics in low- and middle-income countries. Many access antibiotics were unavailable in a majority of most health-care facilities

Is 24 hour observation in hospital after stopping intravenous antibiotics in neonates justified?

Background: Antibiotics are given empirically for suspected sepsis in up to 75% of neonates on the Neonatal and Paediatric Intensive Care Unit (NPICU), after completion of a septic screen. Treatment is discontinued on day 3 if cultures remain negative or after 7-14 days with proven sepsis and, until recently, these neonates are then observed for an additional period of 24 hours before being discharged from hospital. Aim: To assess whether the 24 hour observation period after stopping antibiotics is clinically justified and, if not, whether neonates can be discharged safely on the same day when antibiotics are stopped. Methods: A consecutive sample of 95 babies admitted to NPICU, and who received antibiotics, from December 2006 to January 2008 were analysed prospectively. Their clinical presentation, predisposing risk factors for neonatal sepsis, investigations, antibiotic details and medical management including respiratory support were recorded, and correlated with all events that may have occurred during the observation period after stopping antibiotics. Results: No adverse events were documented in the 24 hour period after antibiotics in all 95 neonates in this study and, therefore, there was no association with any potential predisposing risk factors. Conclusion: The need to observe neonates for a period prior to discharge after stopping antibiotics is not supported on clinical grounds and, as a result of this study, has been discontinued. Neonates can be discharged from hospital safely and immediately on stopping antibiotics, thus reducing hospital stay and an estimated cost saving of approximately €18,000 to the service provider per annum.peer-reviewe